Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease,Endocrine Connections

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Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease
Endocrine Connections ( IF 2.9 ) Pub Date : 2024-01-01 , DOI: 10.1530/ec-23-0161
Iben Rix _{1,

2} , Marie L Johansen ₃ , Asger Lund ₁ , Malte P Suppli ₁ , Elizaveta Chabanova ₄ , Gerrit van Hall _{5,

6} , Jens J Holst _{6,

7} , Nicolai J Wewer Albrechtsen _{6,

8,

9} , Caroline Kistorp _{10,

11} , Filip K Knop _{1,

7,

11,

12}

Affiliation

Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Zealand Pharma A/S, Søborg, Denmark.
Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Department of Radiology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Clinical Metabolomics Core Facility, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Steno Diabetes Center Copenhagen, Herlev, Denmark.

Aims

Hyperglucagonaemia contributes to the pathophysiology in type 2 diabetes (T2D), but the mechanisms behind the inappropriate glucagon secretion are not fully understood. Glucagon and amino acids are regulated in a feedback loop referred to as the liver–α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver–α cell axis resulting in hyperglucagonaemia and hyperaminoacidaemia. We investigated the associations between circulating glucagon, amino acids, and liver fat content in a cohort of individuals with T2D.

Methods

We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using ¹H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses.

Results

Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). The positive association between plasma glucagon concentrations and liver fat content was confirmed in the multivariable regression analyses. Plasma concentrations of isoleucine and glutamate were increased, and glycine and serine concentrations were decreased in individuals with NAFLD. Concentrations of other amino acids were similar between individuals with and without NAFLD, and no clear association was seen between liver fat content and amino acids in the regression analyses.

Conclusion

MRS-diagnosed NAFLD in T2D is associated with hyperglucagonaemia and elevated plasma concentrations of isoleucine and glutamate and low plasma concentrations of glycine and serine. Whether NAFLD and glucagon resistance per se induce these changes remains to be elucidated.

中文翻译：

2 型糖尿病和非酒精性脂肪肝患者的高胰高血糖素血症和氨基酸改变

目标

高胰高血糖素血症与 2 型糖尿病 (T2D) 的病理生理学有关，但胰高血糖素分泌不当背后的机制尚不完全清楚。胰高血糖素和氨基酸在称为肝-α细胞轴的反馈回路中受到调节。患有非酒精性脂肪性肝病 (NAFLD) 的个体似乎具有胰高血糖素抵抗性，会破坏肝脏 - α 细胞轴，导致高胰高血糖素血症和高氨基酸血症。我们研究了一组 T2D 患者循环胰高血糖素、氨基酸和肝脏脂肪含量之间的关联。

方法

我们在这项横断面研究中纳入了 110 名 T2D 患者。^使用1 H 磁共振波谱 (MRS)对肝脏脂肪含量进行定量。通过多元线性回归分析估计肝脏脂肪含量分别与血浆胰高血糖素和氨基酸之间的关联。

结果

患有 NAFLD 的个体 ( n = 52) 的血浆胰高血糖素浓度高于没有 NAFLD 的个体 ( n = 58)。多变量回归分析证实了血浆胰高血糖素浓度与肝脏脂肪含量之间的正相关性。NAFLD 患者的血浆异亮氨酸和谷氨酸浓度升高，甘氨酸和丝氨酸浓度降低。患有和不患有 NAFLD 的个体之间其他氨基酸的浓度相似，并且在回归分析中没有发现肝脏脂肪含量和氨基酸之间存在明确的关联。